THALES Investigators
As with many secondary prevention stroke trials, the primary efficacy outcome of THALES included events also counted in the primary safety outcome. We sought to disentangle risk and benefit more clearly, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit.
In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk TIA, patients were randomized 1:1 within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin (ticagrelor-aspirin) or matching placebo plus aspirin (NCT03354429). For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or non-hemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these two endpoints.
Among 11,016 patients randomized, a major ischemic event occurred in 5.3% of patients in the ticagrelor-aspirin group and in 6.5% in the aspirin group (absolute risk reduction 1.19%, 95% CI 0.31%-2.07%). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and in 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29%, 95% CI 0.10%-0.48%). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97%, 95% CI 0.08%-1.87%). Findings were similar when different thresholds for disability were applied and for a series of predefined subgroups.
In patients with mild-moderate ischemic stroke or high-risk TIA on aspirin, the ischemic benefits of 30-day treatment with ticagrelor outweigh the risks of hemorrhage.
NCT03354429